Conclusions
Our findings provide a novel role of NgBR in modulating TGF-β1-induced EMT and propose NgBR as a new therapeutic target for treating NSCLC patients.
Methods
TGF-β1 was used to induce EMT process of NSCLC cells. The biological functions of NgBR in promoting TGF-β1-induced NSCLC metastasis were studied by gain- and loss-of-function assays both in vitro and in vivo. The underlying mechanisms were studied using molecular biology assays.
Objective
Metastasis is the leading cause of death in patients with advanced non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) is a crucial event in the metastasis of NSCLC. Our previous works demonstrated that NgBR promoted EMT in NSCLC. However, the molecular mechanism was unclear.
Results
We found that knockdown of NgBR inhibited TGF-β1-induced cell migration and invasion in NSCLC cells. In contrast, NgBR overexpression promoted TGF-β1-induced EMT of A549 cells. Mechanically, we found that knockdown of NgBR facilitated ubiquitination and degradation of TβRI, leading to downregulation of TβRI expression in NSCLC cells. Moreover, we confirmed a positive correlation between NgBR and TβRI in NSCLC tissues. Conclusions: Our findings provide a novel role of NgBR in modulating TGF-β1-induced EMT and propose NgBR as a new therapeutic target for treating NSCLC patients.